Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin

Polina Kameneva, Artem V. Artemov, Maria Eleni Kastriti, Louis Faure, Thale K. Olsen, Jörg Otte, Alek Erickson, Bettina Semsch, Emma R. Andersson, Michael Ratz, Jonas Frisén, Arthur S. Tischler, Ronald R. de Krijger, Thibault Bouderlique, Natalia Akkuratova, Maria Vorontsova, Oleg Gusev, Kaj Fried, Erik Sundström, Shenglin MeiPer Kogner, Ninib Baryawno, Peter V. Kharchenko, Igor Adameyko

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

45 Citaten (Scopus)

Samenvatting

Characterization of the progression of cellular states during human embryogenesis can provide insights into the origin of pediatric diseases. We examined the transcriptional states of neural crest– and mesoderm-derived lineages differentiating into adrenal glands, kidneys, endothelium and hematopoietic tissue between post-conception weeks 6 and 14 of human development. Our results reveal transitions connecting the intermediate mesoderm and progenitors of organ primordia, the hematopoietic system and endothelial subtypes. Unexpectedly, by using a combination of single-cell transcriptomics and lineage tracing, we found that intra-adrenal sympathoblasts at that stage are directly derived from nerve-associated Schwann cell precursors, similarly to local chromaffin cells, whereas the majority of extra-adrenal sympathoblasts arise from the migratory neural crest. In humans, this process persists during several weeks of development within the large intra-adrenal ganglia-like structures, which may also serve as reservoirs of originating cells in neuroblastoma.

Originele taal-2Engels
Pagina's (van-tot)694-706
Aantal pagina's13
TijdschriftNature Genetics
Volume53
Nummer van het tijdschrift5
DOI's
StatusGepubliceerd - mei 2021

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